Activation of renal vascular smooth muscle TRPV4 channels by 5-hydroxytryptamine impairs kidney function in neonatal pigs

Microvasc Res. 2023 Jul:148:104516. doi: 10.1016/j.mvr.2023.104516. Epub 2023 Mar 6.


Control of microvascular reactivity by 5-hydroxytryptamine (5-HT; serotonin) is complex and may depend on vascular bed type and 5-HT receptors. 5-HT receptors consist of seven families (5-HT1-5-HT7), with 5-HT2 predominantly mediating renal vasoconstriction. Cyclooxygenase (COX) and smooth muscle intracellular Ca2+ levels ([Ca2+]i) have been implicated in 5-HT-induced vascular reactivity. Although 5-HT receptor expression and circulating 5-HT levels are known to be dependent on postnatal age, control of neonatal renal microvascular function by 5-HT is unclear. In the present study, we demonstrate that 5-HT stimulated human TRPV4 transiently expressed in Chinese hamster ovary cells. 5-HT2A is the predominant 5-HT2 receptor subtype in freshly isolated neonatal pig renal microvascular smooth muscle cells (SMCs). HC-067047 (HC), a selective TRPV4 blocker, attenuated cation currents induced by 5-HT in the SMCs. HC also inhibited the 5-HT-induced increase in renal microvascular [Ca2+]i and constriction. Intrarenal artery infusion of 5-HT had minimal effects on systemic hemodynamics but reduced renal blood flow (RBF) and increased renal vascular resistance (RVR) in the pigs. Transdermal measurement of glomerular filtration rate (GFR) indicated that kidney infusion of 5-HT reduced GFR. HC and 5-HT2 receptor antagonist ritanserin attenuated 5-HT effects on RBF, RVR, and GFR. Moreover, the serum and urinary COX-1 and COX-2 levels in 5-HT-treated piglets were unchanged compared with the control. These data suggest that activation of renal microvascular SMC TRPV4 channels by 5-HT impairs kidney function in neonatal pigs independently of COX production.

Keywords: 5-HT; Neonatal kidney function; Renal vasoregulation; TRPV4.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • CHO Cells
  • Cricetinae
  • Cricetulus
  • Humans
  • Infant, Newborn
  • Kidney / blood supply
  • Muscle, Smooth, Vascular* / metabolism
  • Receptors, Serotonin / metabolism
  • Serotonin*
  • Swine
  • TRPV Cation Channels / metabolism


  • Serotonin
  • TRPV Cation Channels
  • Receptors, Serotonin
  • TRPV4 protein, human